This proposal describes a Phase I research study to test feasibility of using an ultra-miniaturized protein NanoArray for analysis of premalignant conversion and therapeutic monitoring in human cancer biopsy samples. BioForce Laboratory, Inc. will conduct this study in collaboration with the FDA-NCI clinical proteomics program, whose objective is to catalogue proteomic changes occurring during cancer I progression, and use this information to revolutionize diagnosis and treatment through individualized molecular medicine. This target requires the availability of a reliable, cost-effective assay that can generate accurate protein profiles from exceedingly limited quantities of patient tissue. In the first stage current reverse-phase microarray techniques wiII be adapted for use in the NanoArray format. We will analyze precision, linearity and limits of marker detection using purified antigen and validated antibodies. In the second stage we will validate the NanoArray technology using a previously defined esophageal cancer system. This stage will utilize actual laser capture microdissected cell populations derived from patient-matched, progressive stages of malignant esophageal cancer. These samples will be provided to BioForce from the FDA-NCI clinical proteomics researchers. Phase II studies will involve screening of a wider variety of cancers using a larger set of markers. We anticipate that experimental data generated in a large-scale Phase II study will lead to the identification of cancer-specific, clinically relevant markers and entire signal pathways. This could become the foundation for new diagnostic and therapeutic approaches that wilI be the basis for construction of commercial diagnostic tools for the oncology market and will be integral to therapeutic management by the treating physician.